Peringatan Keamanan

Oral LD50 value in rats is 7,060 mg/kg and 3,450 mg/kg in mouse. Adverse effects include anemia, cough, CNS depression, drowsiness, headache, heart damage, lassitude (weakness, exhaustion), liver damage, narcosis, reproductive effects and teratogenic effects.

Doconexent

DB03756

small molecule approved investigational

Deskripsi

A mixture of fish oil and primrose oil, doconexent is used as a high-docosahexaenoic acid (DHA) supplement. DHA is a 22 carbon chain with 6 cis double bonds with anti-inflammatory effects. It can be biosythesized from alpha-linolenic acid or commercially manufactured from microalgae. It is an omega-3 fatty acid and primary structural component of the human brain, cerebral cortex, skin, and retina thus plays an important role in their development and function. The amino-phospholipid DHA is found at a high concentration across several brain subcellular fractions, including nerve terminals, microsomes, synaptic vesicles, and synaptosomal plasma membranes A19436.

Struktur Molekul 2D

Berat 328.4883
Wujud liquid

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) Approximately 20 hours [A19370].
Volume Distribusi DHA is the most abundant n?3 fatty acid in membranes and is present in all organs. It is also the most variable among organs and is particularly abundant in neural tissue, such as brain and retina, where it is several hundred-fold more abundant than EPA [A19452].
Klirens (Clearance) -

Absorpsi

Like other omega-3 fatty acids, DHA is hydrolyzed from the intestines and delivered through the lymphatic circulation. Plasma DHA concentrations increase in a dose-dependent and saturable manner.

Metabolisme

DHA can be metabolized into DHA-derived specialized pro-resolving mediators (SPMs), DHA epoxides, electrophilic oxo-derivatives (EFOX) of DHA, neuroprostanes, ethanolamines, acylglycerols, docosahexaenoyl amides of amino acids or neurotransmitters, and branched DHA esters of hydroxy fatty acids, among others. It is converted to 17-hydroperoxy-DHA derivatives via COX-2 and 15-LOX and 5-LOX activity. These derivatives are further converted into D-series resolvins and protectins with potent anti-inflammatory potential and potent neuroprotective effect A19431. DHA may also be metabolized to 19,20-epoxydocosapentaenoic acids (EDPs) and isomers via CYP2C9 activity. Epoxy metabolites are reported to mediate anti-tumor activity by inhibiting angiogenesis, tumor growth, and metastasis.

Rute Eliminasi

Data eliminasi belum tersedia.

Interaksi Obat

326 Data
Ibrutinib Doconexent may increase the antiplatelet activities of Ibrutinib.
Fluvoxamine The metabolism of Doconexent can be decreased when combined with Fluvoxamine.
Troglitazone The metabolism of Doconexent can be decreased when combined with Troglitazone.
Fluoxetine The metabolism of Doconexent can be decreased when combined with Fluoxetine.
Nabilone The metabolism of Nabilone can be decreased when combined with Doconexent.
Imatinib The metabolism of Doconexent can be decreased when combined with Imatinib.
Efavirenz The metabolism of Doconexent can be decreased when combined with Efavirenz.
Mifepristone The metabolism of Doconexent can be decreased when combined with Mifepristone.
Felbamate The metabolism of Doconexent can be decreased when combined with Felbamate.
Amiodarone The metabolism of Doconexent can be decreased when combined with Amiodarone.
Sulfinpyrazone The metabolism of Doconexent can be decreased when combined with Sulfinpyrazone.
Iproniazid The metabolism of Doconexent can be decreased when combined with Iproniazid.
Medical Cannabis The metabolism of Doconexent can be decreased when combined with Medical Cannabis.
Valproic acid The metabolism of Doconexent can be decreased when combined with Valproic acid.
Quinidine The metabolism of Doconexent can be decreased when combined with Quinidine.
Dabrafenib The serum concentration of Doconexent can be decreased when it is combined with Dabrafenib.
Fluconazole The metabolism of Doconexent can be decreased when combined with Fluconazole.
Floxuridine The metabolism of Doconexent can be decreased when combined with Floxuridine.
Nicardipine The metabolism of Doconexent can be decreased when combined with Nicardipine.
Delavirdine The metabolism of Doconexent can be decreased when combined with Delavirdine.
Miconazole The metabolism of Doconexent can be decreased when combined with Miconazole.
Gemfibrozil The metabolism of Doconexent can be decreased when combined with Gemfibrozil.
Sulfaphenazole The metabolism of Doconexent can be decreased when combined with Sulfaphenazole.
Bosentan The metabolism of Doconexent can be increased when combined with Bosentan.
Enzalutamide The serum concentration of Doconexent can be decreased when it is combined with Enzalutamide.
Peginterferon alfa-2b The metabolism of Doconexent can be increased when combined with Peginterferon alfa-2b.
Apalutamide The serum concentration of Doconexent can be decreased when it is combined with Apalutamide.
Delafloxacin The metabolism of Doconexent can be increased when combined with Delafloxacin.
Ritonavir The metabolism of Doconexent can be increased when combined with Ritonavir.
Valsartan The metabolism of Doconexent can be decreased when combined with Valsartan.
Bortezomib The metabolism of Bortezomib can be decreased when combined with Doconexent.
Torasemide The metabolism of Doconexent can be decreased when combined with Torasemide.
Nevirapine The metabolism of Nevirapine can be decreased when combined with Doconexent.
Diethylstilbestrol The metabolism of Doconexent can be decreased when combined with Diethylstilbestrol.
Sulfisoxazole The metabolism of Doconexent can be decreased when combined with Sulfisoxazole.
Sulfadiazine The metabolism of Doconexent can be decreased when combined with Sulfadiazine.
Progesterone The metabolism of Doconexent can be decreased when combined with Progesterone.
Cerivastatin The metabolism of Doconexent can be decreased when combined with Cerivastatin.
Teniposide The metabolism of Doconexent can be decreased when combined with Teniposide.
Lansoprazole The metabolism of Lansoprazole can be decreased when combined with Doconexent.
Cimetidine The metabolism of Doconexent can be decreased when combined with Cimetidine.
Fluorouracil The metabolism of Doconexent can be decreased when combined with Fluorouracil.
Zafirlukast The metabolism of Doconexent can be decreased when combined with Zafirlukast.
Sulfamethizole The metabolism of Doconexent can be decreased when combined with Sulfamethizole.
Voriconazole The metabolism of Voriconazole can be decreased when combined with Doconexent.
Medroxyprogesterone acetate The metabolism of Doconexent can be decreased when combined with Medroxyprogesterone acetate.
Amodiaquine The metabolism of Doconexent can be decreased when combined with Amodiaquine.
Oxandrolone The metabolism of Doconexent can be decreased when combined with Oxandrolone.
Simvastatin The metabolism of Doconexent can be decreased when combined with Simvastatin.
Nilutamide The metabolism of Doconexent can be decreased when combined with Nilutamide.
Epinephrine The metabolism of Doconexent can be decreased when combined with Epinephrine.
Paroxetine The metabolism of Doconexent can be decreased when combined with Paroxetine.
Modafinil The metabolism of Doconexent can be decreased when combined with Modafinil.
Tranylcypromine The metabolism of Doconexent can be decreased when combined with Tranylcypromine.
Clopidogrel The metabolism of Doconexent can be decreased when combined with Clopidogrel.
Methimazole The metabolism of Doconexent can be decreased when combined with Methimazole.
Phenylbutazone The metabolism of Doconexent can be decreased when combined with Phenylbutazone.
Sulfapyridine The metabolism of Doconexent can be decreased when combined with Sulfapyridine.
Ethanol The metabolism of Doconexent can be decreased when combined with Ethanol.
Metronidazole The metabolism of Doconexent can be decreased when combined with Metronidazole.
Isoniazid The metabolism of Doconexent can be decreased when combined with Isoniazid.
Azelastine The metabolism of Azelastine can be decreased when combined with Doconexent.
Sulfamethoxazole The metabolism of Doconexent can be decreased when combined with Sulfamethoxazole.
Glyburide The metabolism of Doconexent can be decreased when combined with Glyburide.
Felodipine The metabolism of Doconexent can be decreased when combined with Felodipine.
Fenofibrate The metabolism of Doconexent can be decreased when combined with Fenofibrate.
Promethazine The metabolism of Doconexent can be decreased when combined with Promethazine.
Fluvastatin The metabolism of Doconexent can be decreased when combined with Fluvastatin.
Leflunomide The metabolism of Doconexent can be decreased when combined with Leflunomide.
Sertraline The metabolism of Doconexent can be decreased when combined with Sertraline.
Atovaquone The metabolism of Doconexent can be decreased when combined with Atovaquone.
Cyclizine The metabolism of Doconexent can be decreased when combined with Cyclizine.
Flecainide The metabolism of Doconexent can be decreased when combined with Flecainide.
Ginkgo biloba The metabolism of Doconexent can be decreased when combined with Ginkgo biloba.
Pranlukast The metabolism of Doconexent can be decreased when combined with Pranlukast.
Etoricoxib The metabolism of Doconexent can be decreased when combined with Etoricoxib.
Genistein The metabolism of Doconexent can be decreased when combined with Genistein.
Topiroxostat The metabolism of Doconexent can be decreased when combined with Topiroxostat.
Sildenafil The metabolism of Sildenafil can be decreased when combined with Doconexent.
Eletriptan The metabolism of Eletriptan can be decreased when combined with Doconexent.
Glimepiride The metabolism of Glimepiride can be decreased when combined with Doconexent.
Dapsone The metabolism of Dapsone can be decreased when combined with Doconexent.
Desogestrel The metabolism of Desogestrel can be decreased when combined with Doconexent.
Bexarotene The metabolism of Bexarotene can be decreased when combined with Doconexent.
Amitriptyline The metabolism of Amitriptyline can be decreased when combined with Doconexent.
Hydromorphone The metabolism of Hydromorphone can be decreased when combined with Doconexent.
Indomethacin The metabolism of Indomethacin can be decreased when combined with Doconexent.
Methadone The metabolism of Methadone can be decreased when combined with Doconexent.
Diltiazem The metabolism of Diltiazem can be decreased when combined with Doconexent.
Trimethadione The metabolism of Trimethadione can be decreased when combined with Doconexent.
Clozapine The metabolism of Clozapine can be decreased when combined with Doconexent.
Treprostinil The metabolism of Treprostinil can be decreased when combined with Doconexent.
Rosiglitazone The metabolism of Rosiglitazone can be decreased when combined with Doconexent.
Acetohexamide The metabolism of Acetohexamide can be decreased when combined with Doconexent.
Promazine The metabolism of Promazine can be decreased when combined with Doconexent.
Zolpidem The metabolism of Zolpidem can be decreased when combined with Doconexent.
Trimethoprim The metabolism of Trimethoprim can be decreased when combined with Doconexent.
Nabumetone The metabolism of Nabumetone can be decreased when combined with Doconexent.
Quinine The metabolism of Quinine can be decreased when combined with Doconexent.
Tenoxicam The metabolism of Tenoxicam can be decreased when combined with Doconexent.

Target Protein

Peroxisome proliferator-activated receptor alpha PPARA
Prostaglandin G/H synthase 1 PTGS1
Prostaglandin G/H synthase 2 PTGS2
Peroxisome proliferator-activated receptor gamma PPARG
Retinoic acid receptor RXR-alpha RXRA
Retinoic acid receptor RXR-beta RXRB
Retinoic acid receptor RXR-gamma RXRG
Sterol regulatory element-binding protein 1 SREBF1
Myc proto-oncogene protein MYC

Referensi & Sumber

Artikel (PubMed)
  • PMID: 22254027
    Calder PC: Omega-3 fatty acids and inflammatory processes. Nutrients. 2010 Mar;2(3):355-74. doi: 10.3390/nu2030355. Epub 2010 Mar 18.
  • PMID: 17488715
    Kim HY: Novel metabolism of docosahexaenoic acid in neural cells. J Biol Chem. 2007 Jun 29;282(26):18661-5. Epub 2007 May 8.
  • PMID: 20422316
    Picq M, Chen P, Perez M, Michaud M, Vericel E, Guichardant M, Lagarde M: DHA metabolism: targeting the brain and lipoxygenation. Mol Neurobiol. 2010 Aug;42(1):48-51. doi: 10.1007/s12035-010-8131-7. Epub 2010 Apr 28.
  • PMID: 16899822
    Butovich IA, Lukyanova SM, Bachmann C: Dihydroxydocosahexaenoic acids of the neuroprotectin D family: synthesis, structure, and inhibition of human 5-lipoxygenase. J Lipid Res. 2006 Nov;47(11):2462-74. Epub 2006 Aug 9.
  • PMID: 16424216
    Serhan CN, Gotlinger K, Hong S, Lu Y, Siegelman J, Baer T, Yang R, Colgan SP, Petasis NA: Anti-inflammatory actions of neuroprotectin D1/protectin D1 and its natural stereoisomers: assignments of dihydroxy-containing docosatrienes. J Immunol. 2006 Feb 1;176(3):1848-59.
  • PMID: 22912397
    Mas E, Croft KD, Zahra P, Barden A, Mori TA: Resolvins D1, D2, and other mediators of self-limited resolution of inflammation in human blood following n-3 fatty acid supplementation. Clin Chem. 2012 Oct;58(10):1476-84. Epub 2012 Aug 21.
  • PMID: 26511533
    Chen CT, Kitson AP, Hopperton KE, Domenichiello AF, Trepanier MO, Lin LE, Ermini L, Post M, Thies F, Bazinet RP: Plasma non-esterified docosahexaenoic acid is the major pool supplying the brain. Sci Rep. 2015 Oct 29;5:15791. doi: 10.1038/srep15791.
  • PMID: 11483627
    Pawlosky RJ, Hibbeln JR, Novotny JA, Salem N Jr: Physiological compartmental analysis of alpha-linolenic acid metabolism in adult humans. J Lipid Res. 2001 Aug;42(8):1257-65.
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